title: The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.
abstract: OBJECTIVE
  In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI.
  
  
  METHODS
  Follow-up observational study at two CHI referral hospitals.
  
  
  METHODS
  Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI.
  
  
  RESULTS
  In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy.
  
  
  CONCLUSIONS
  Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK. indi.banerjee@cmft.nhs.uk
authors.forename: I
authors.initials: I
authors.lastname: Banerjee
authors.forename: M
authors.initials: M
authors.lastname: Skae
authors.forename: S E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: L
authors.initials: L
authors.lastname: Rigby
authors.forename: L
authors.initials: L
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: Didi
authors.forename: J
authors.initials: J
authors.lastname: Blair
authors.forename: S
authors.initials: S
authors.lastname: Ehtisham
authors.forename: S
authors.initials: S
authors.lastname: Ellard
authors.forename: K E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: P E
authors.initials: PE
authors.lastname: Clayton
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D044903:Congenital Hyperinsulinism / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D019468:Disease Management; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D013997:Time Factors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel